User talk:Jcjjhrsms
Thanks Janell - See you in class.Digbymom (talk) 13:26, 5 December 2008 (UTC)
Stem cell therapeutics in animals
[edit]Veterinary applications and their contributions to human medicine
[edit]- Research currently conducted on horses, dogs, and cats can benefit the development of stem-cell treatments in veterinary medicine, but may also contribute to developing those in human medicine for a range injuries and diseases such as myocardial infarction, stroke, tendon and ligament damage, osteoarthritis, osteochondrosis and muscular dystrophy.[1][2][3][4] Research into using stem cells for therapeutic purposes generally reflects human medical needs, but the high degree of frequency and severity of certain injuries in racehorses has put veterinary medicine at the forefront of this novel regenerative approach.[5] Companion animals may be superior models than typical mouse models for human disease. [6][7]
Veterinary research has developed regenerative treatment models, particularly involving mesenchymal stem cells
[edit]- Veterinary applications of stem cell therapy as a means of regenerating new tissue as an alternative to scar (less functional tissue) formation have developed from research that has been conducted since 1998 using adult-derived mesenchymal stem cells to treat animals with injuries or defects affecting bone, cartilage, ligaments and/or tendons.[8] [9][10]Because mesenchymal stem cells can differentiate into the cells that make up bone, cartilage, tendons, and ligaments (as well as muscle, fat, and possibly other tissues), they have been the main type of stem cells studied in the treatment of diseases affecting these tissues.[11][12]The two main sources of mesenchymal stem cells used are adipose (fat) tissue or bone marrow. Because an animal's immune system mounts a detrimental response to transplanted cells, except in the case of cells from a very closely genetically related individual, therapeutic stem cells are most often derived from the patient prior to therapy.[13] [14][15]These are termed autologous stem cells. In surgical repair of bone fractures, veterinarians have found that grafting mesenchymal stem cells from a genetically different donor of the same species, termed allogeneic mesenchymal stem cells, does not elicit an immunological response in the patient and can be used to help regenerate bone tissue in major bony fractures and defects.[16] [17]Stem cells can help speed the repair of bone fractures and defects that would normally require extensive grafting and mesenchymal stem cell use in surgical implants may actually be superior to traditional grafting techniques.[16] [17]
The significance of stem cell microenvironments
[edit]- To regenerate bone, stem cells must be in a carrier system that provides the appropriate context: a scaffold, upon which the introduced stem cells develop, the minerals needed to develop properly into functional bone, and growth factors that signal to the mesenchymal stem cell to differentiate into bone cells.[18][17][15][19] Whether the stem cells are to heal bone or any other type of tissue, the context or microenvironment in which a group of introduced stem cells is placed is essential for effective healing, not only to provide growth factors and other chemical signals that guide appropriate differentiation of the mesenchymal stem cells, but also to ensure that they remain directed to the appropriate site and are able to emit their appropriate signals and make appropriate cell contacts. This aids healing in three ways: 1) helping the formation of new blood cells from endothelial progenitor cells, which are different type of stem cells that need to be in the regenerative cell mixture or available in the nearby host tissue; 2) preventing programed cell death or apoptosis of cells at the damaged site; and 3) reducing inflammation. [18][15][17]Often platelet-rich plasma is used in conjunction with bone-marrow derived stem cells as a matrix which supplies growth factors and the scaffold needed to induce tissue regeneration.[15][19] Alternatively, adipose tissue contains not only mesenchymal stem cells, but also other diverse types of cells that can provide the microenvironment that supports tissue regeneration without additional factors.[20][21][13]
Sources of autologous (patient-derived) mesenchymal stem cells
[edit]- Autologous stem cells intended for regenerative therapy are either taken from the patient's bone marrow or from adipose tissue. The number of stem cells applied to the damaged tissue is important for effective therapy. For this reason, stem cells derived from bone marrow aspirates, which are normally in numbers too small to elicit a regenerative effect, are cultured in specialized laboratories to expand their numbers to be in the millions before use in regenerative therapy. [19][17]Although adipose-derived tissue also needs processing prior to use in regnerative therapy, the time-consuming culturing like that needed currently for bone marrow derived mesenchymal stem cells, is not required, thus reducing the time between collection and implantation in autologous stem cell treatments.[22][23] Although mesenchymal stem cells from any source have the potential to differentiate into a diverse range of tissues expert opinions vary as to which source is preferable in particular applications. Some have expressed bone-marrow derived stem cells are particularly preferred for bone, cartilage, ligament, and tendon repair; while others find the ease of collection and the multi-cellular microenvironment already present in adipose-derived stem cell fractions make fat the preferred source.[15][13][14]
Currently Available Treatments for Horses and Dogs Suffering from Orthopedic Conditions
[edit]- Autologous or allogeneic stem cells are currently used as an adjunctive therapy in the surgical repair of some types of fractures in dogs and horses.[17][24]Autologous stem cell-based treatments for ligament injury, tendon injury, osteoarthritis, osteochondrosis, and sub-chondral bone cysts have been commercially available to practicing veterinarians to treat horses since 2003 in the United States and since 2006 in the United Kingdom.[13][14]Autologous stem-cell based treatments for tendon injury, ligament injury, and osteoarthritis in dogs have been available to veterinarians in the United States since 2005.[13] Over 3000 privately-owned horses and dogs have been treated with autologous adipose-derived stem cells.[13] The efficacy of these treatments has been shown in double-blind clinical trials for dogs with osteoarthritis of the hip and elbow and horses with tendon damage[25][26] The efficacy of using stem cells, whether adipose-derived or bone-marrow derived, for treating tendon and ligament injuries in horses has support in the veterinary literature.[27][28]Although more specific characterization and localization studies of the stem-cell containing fractions used in regenerative medicine have been identified as necessary in the veterinary literature, there is scientific evidence supporting that stem cells provide an antiinflammatory effect, stimulate healing by homing to damaged tissues and recruiting other necessary cells for necessary healing, such as endothelial progenitor cells, support tissue remodeling over scar formation, inhibit apoptosis, and are capable of differentiating into bone, cartilage, tendon, and ligament tissue.[29][30]
Developments in Stem Cell Treatments in Veterinary Internal Medicine
[edit]- Currently, research is being conducted to develop stem cell treatments for horses suffering from COPD, neurologic disease, and laminitis and for dogs and cats suffering from heart disease, liver disease, kidney disease, neurologic disease, and immune-mediated disorders.[31]
(feline renal dz trials,COPD in horses, vet-stem projects, immunological study, and the before referenced cardiac, neural, genetic dz advances)
Cancer
[edit]Stem cell therapy not recommended for patients with known or high likelihood of developing cancer-(vet stem, other cautionary cancer article) However in the context of an allogenic bone marrow transplant following complete radiation-mediated destruction of diseased bone marrow, bone marrow stem cells have been used to treat dogs. (bone marrow transplant article)
Cautions and Limitations
[edit](what vet stem recommends NOT to do-especially since immunomodulary function of stem cells means no infection can be present at site, also genetic and diffuse maladies are not beneficial targets for stem cell therapy (more research needed Dvm equine article, canaadian article, mimeaut article, cartilage study in horses)
- ^ Chen J, Li Y, Wang L, Zhang Z, Lu D, Lu M, Chopp M. Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke. 2001; 32: 1005-1011
- ^ Assmus B, Schachinger V, Teupe C, et al. Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation 2002 Dec 10;106(24):3009-17
- ^ Murphy JM, Fink DJ, Hunziker EB, Barry FP. Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum 2003 Dec;48(12):3464-74
- ^ Sampaolesi M, et al. Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs. Nature. 2006: 444:574-579.
- ^ Taylor SE, Smith RKW, Clegg PD (2007). Mesenchymal stem cell therapy in equine musculoskeletal disease: scientific fact or clinical fiction? Equine Veterinary Journal 39 (2). 172-180.
- ^ Tecirlioglu RT, Trounson AO (2007). Embryonic stem cells in companion animals (horses, dogs, and cats): present status and future prospects. Reproduction Fertility and Development 19 (6). 740-747.
- ^ Koch TG, Betts, DH (2007). Stem cell therapy for joint problems using the horse as a clinically relevant animal model. Expert Opin Biol Ther 7(11). 1621-6
- ^ Young RG, Butler DL, Weber W, Caplan AI, Gordon SL, Fink DJ. Use of Mesenchymal Stem Cells in a Collagen Matrix for Achilles Tendon Repair. J Ortho Res 1998 (16): 406.
- ^ Awad HA, Butler DL, Boivin GP, et al. Autologous mesenchymal stem cell-mediated repair of tendon. Tissue Eng 1999; 5 (3): 267.
- ^ Bruder SP, Kraus K, Goldberg V, Kadiyala S: The Effect of Implants Loaded with Autologous Mesenchymal Stem Cells on the Healing of Canine Segmental Bone Defects. The Journal of Bone and Joint Surgery, Incorporated 80-A:985-996, 1998.
- ^ Nathan S, Das De S, Thambyah A, et al. Cell-based therapy in the repair of osteochondral defects: A novel use for adipose tissue. Tissue Eng 2003 Aug;9(4):733-44
- ^ Awad HA, Butler DL, et al. Autologous mesenchymal stem cell-mediated repair of tendon. Tissue Eng 1999 Jun:5(3):267-77.
- ^ a b c d e f http://www.vet-stem.com
- ^ a b c http://www.vetcell.com
- ^ a b c d e Kane, Ed (May 2008). Stem cell therapy shows promise for soft-tissue injury, disease. DVM Newsmagazine. 6E-10E.
- ^ a b Kraus K, Kirker-Head C (2006). Mesenchymal stem cells and bone regeneration. Veterinary Surgery 35 (3). 232-242
- ^ a b c d e f Zachos TA, Smith TJ (September 2008). Use of adult stem cells in clinical orthopedics. DVM Newsmagazine. 36-39.
- ^ a b Singec, I, et al. The leading edge of stem cell therapeutics. Annu Rev Med. 2007. 58:313-328
- ^ a b c Yamada Y, et al. Autogenous injectable bone for regeneration with mesenchymal stem cells and platelet-rich plasma: tissue engineered bone regeneration. Tissue Engineering. 2004. 10(5-6): 955-964.
- ^ Nakagami H, Morishita R, Maeda K, et al. Adipose tissue-derived stromal cells as a novel option for regenerative cell therapy. J Atheroscler Throm 2006 Apr;13(2):77-81
- ^ Oedayrajsingh M, Breuls R, Schouten T, et al. Phenotypical and functional characterization of freshly isolated adipose tissue-derived stem cells. Stem Cells Dev 2007;16:91-104
- ^ Fraser JK, Wulur I, Alfonso Z, et al. Fat Tissue: an underappreciated source of stem cells for biotechnology. Trends Biotechnol 2006 Apr;24(4):150-4.
- ^ Nakagami H, Morishita R, Maeda K, et al. Adipose tissue-derived stromal cells as a novel option for regenerative cell therapy. J Atheroscler Throm 2006 Apr;13(2):77-81
- ^ http://www.thehorse.com/ViewArticle.aspx?ID=13171
- ^ Black L, et al. Effect of intraarticular injection of autologous adipose-derived mesenchymal stem and regenerative cells on clinical signs of chronic osteoarthritis of the elbow joint in dogs. Veterinary Therapeutics. 2008. 9 (3): 192-200
- ^ Nixon A, et al. Effect of adipose-derived nucleated cell fractions on tendon repair in horses with collagenase-induced tendinitis.AJVR. July 2008. 69 (7): 928-937.
- ^ Smith RKW. Principles of stem cell therapy in the horse – the science behind the technology. Pferdeheilkunde. 2008. 24 (4): 508
- ^ Richardson LE, et al. Stem cells in veterinary medicine-attempts at regenerating equine tendon after injury. Trends Biotechnol. 25 (9): 409-416.
- ^ Richardson LE, et al. Stem cells in veterinary medicine-attempts at regenerating equine tendon after injury. Trends Biotechnol. 25 (9): 409-416.
- ^ Csaki C, et al. Chondrogenesis, osteogenesis and adipogenesis of canine mesenchymal stem cells: a biochemical, morphological and ultrastructural study. Histochemistry & Cell Biology. 2007:128 (6) :p507-520.
- ^ www.vet-stem.com